Copper-Catalyzed Asymmetric Cyclizative Sulfinamidation: Forging Indole-Based Stereogenic Sulfur(IV) Centers and Atropisomeric Chirality

IF 10.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Xiaowu Fang, , , Fengrui Xiang, , , Yue Zhao, , and , Zhuangzhi Shi*, 
{"title":"Copper-Catalyzed Asymmetric Cyclizative Sulfinamidation: Forging Indole-Based Stereogenic Sulfur(IV) Centers and Atropisomeric Chirality","authors":"Xiaowu Fang,&nbsp;, ,&nbsp;Fengrui Xiang,&nbsp;, ,&nbsp;Yue Zhao,&nbsp;, and ,&nbsp;Zhuangzhi Shi*,&nbsp;","doi":"10.1021/acscentsci.5c00909","DOIUrl":null,"url":null,"abstract":"<p >The structural prominence of indole-based sulfur-containing compounds in pharmacologically relevant substances stems from their versatile biofunctional capabilities. Despite their significance, the stereogenic elements embedded in these structures have frequently been overlooked in drug discovery endeavors primarily due to the absence of efficient synthetic methodologies. Here, we introduce a groundbreaking strategy for the enantioselective synthesis of indole-based sulfinamides via a copper-catalyzed asymmetric nucleophilic cyclization and sulfinamidation reaction. Utilizing <i>ortho</i>-alkynylanilines and sulfinylamines, this method achieves a broad spectrum of sulfinamides with complete atom economy, establishing a new paradigm in synthetic efficiency. Our approach not only facilitates the formation of S-chirogenic sulfinamides but also concurrently constructs products featuring both stereogenic sulfur and atropisomeric chirality. Comprehensive mechanistic investigations, complemented by density functional theory (DFT) calculations, provide deep insights into the reaction mechanism, particularly in elucidating the S-stereogenic and atropisomeric control during the cyclization and sulfinamidation processes.</p><p >A copper-catalyzed cyclizative sulfinamidation strategy enables facile synthesis of indole-based sulfinamides with simultaneous control of stereogenic sulfur and atropisomeric chirality.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1762–1772"},"PeriodicalIF":10.4000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00909","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Central Science","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acscentsci.5c00909","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

The structural prominence of indole-based sulfur-containing compounds in pharmacologically relevant substances stems from their versatile biofunctional capabilities. Despite their significance, the stereogenic elements embedded in these structures have frequently been overlooked in drug discovery endeavors primarily due to the absence of efficient synthetic methodologies. Here, we introduce a groundbreaking strategy for the enantioselective synthesis of indole-based sulfinamides via a copper-catalyzed asymmetric nucleophilic cyclization and sulfinamidation reaction. Utilizing ortho-alkynylanilines and sulfinylamines, this method achieves a broad spectrum of sulfinamides with complete atom economy, establishing a new paradigm in synthetic efficiency. Our approach not only facilitates the formation of S-chirogenic sulfinamides but also concurrently constructs products featuring both stereogenic sulfur and atropisomeric chirality. Comprehensive mechanistic investigations, complemented by density functional theory (DFT) calculations, provide deep insights into the reaction mechanism, particularly in elucidating the S-stereogenic and atropisomeric control during the cyclization and sulfinamidation processes.

A copper-catalyzed cyclizative sulfinamidation strategy enables facile synthesis of indole-based sulfinamides with simultaneous control of stereogenic sulfur and atropisomeric chirality.

铜催化的不对称环化亚胺化:锻造吲哚基立体硫(IV)中心和atrosomomer手性
吲哚基含硫化合物在药理学相关物质中的结构突出源于其多功能的生物功能能力。尽管它们具有重要意义,但由于缺乏有效的合成方法,嵌入这些结构中的立体元素在药物发现工作中经常被忽视。在这里,我们介绍了一种突破性的策略,通过铜催化的不对称亲核环化和亚砜化反应对映选择性合成吲哚基亚砜酰胺。该方法利用邻炔苯胺和亚砜胺,实现了广谱亚砜胺的合成,具有完全的原子经济性,开创了合成效率的新模式。我们的方法不仅促进了s -氨基亚胺的形成,而且同时构建了具有立体性和atrosomomer手性的产物。综合机理研究,结合密度泛函理论(DFT)计算,提供了对反应机理的深入了解,特别是阐明了环化和亚砜化过程中的s -立体和atrosom异构控制。铜催化的环化亚砜化策略可以方便地合成吲哚基亚砜胺,同时控制立体性硫和atroisomer手性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
ACS Central Science
ACS Central Science Chemical Engineering-General Chemical Engineering
CiteScore
25.50
自引率
0.50%
发文量
194
审稿时长
10 weeks
期刊介绍: ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信